Yong Meng Hsien Lecturer & Ophthalmologist, UKM & HCTM, Malaysia yongmenghsien@ppukm.ukm.edu.my Last edited: Feb 202

1. Ophthalmic Tumours
Dr Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM
yongmenghsien@ppukm.ukm.edu.my
Last edited: Feb 2022

2. Ophthalmic Tumours
• Primary VS Secondary
• Orbital VS Ocular
• Benign VS Malignant
• Childhood VS Adult
• Congenital VS Acquired
• Hamartoma VS Choristoma
• Infiltrative (leukemia lymphoma)
• Association
– Systemic/syndrome/phacomatoses

3. Ophthalmic Tumours
Orbital
• Eyelid
• Lacrimal gland
• ON/vascular/lymphoid
• Orbital soft tissue
• Orbital bone
Ocular
• Ocular surface/ conjunctival
• Uveal
• Retinal (nerve/vascular/cell)
• Choroid (vascular/cell)
• ON

4. Benign Lesion- Key
• stable size/shape/colour/border
• lack of induration/ulceration/hrge/change
• preservation of normal structures
• Histo: no hyperchromatism, pleomorphism,
mitotic figures, high nucleus-cytoplasm ratio

5. Pathology/Biopsy- Principles
• Tissue
– Incisional vs excisional (shave/simple/Mohs)
• Permanent section (formalin 10%- reduce autolysis)
• Frozen section (wet gauze): intraop complete
excision/margin free, correct sample for permanent section
• Fresh section (wet gauze): lymphoproliferative d/o for
flow cytometry/cell marker study
• Others fixative: glutaraldehyde (rapid stabilize protein-
good for ECM/cytoplasm), ethyl alcohol (good for
cytology/nuclear details)
• Cells
– FNAC

6. Orbital Tumour- Orbit

7. Orbital Tumour
• Anatomical
• Eyelid
• Lacrimal
• Vascular/Nerve/Lymphatic
• Soft tissue/cyst
• Childhood VS Adult
• Hamartoma VS Choristoma
• Primary VS Secondary (local spread/metastasis)
• DDX:
• Infiltration: lymphoma/leukemia
• Infection: cellulitis, dacryoadenitis/cystitis, TB/fungal
• Inflammation: TED/vasculitis/sarcoid/IgG4/pseudotumour

8. Orbital Mass- Features
• Sup temporal mass
– Lacrimal gland (prolapsed/tumour)
– Dermoid cyst
– NSOI
– Lymphoma
– Orbital fat
– Dermolipoma
– Conj papilloma
• Sup nasal mass
– Dermoid cyst
– Meningo-encephalo-cele
– Mucocele
– NF
– RMS
– Lymphoma
• Proptosis: axial/non axial (dystopia/diplopia)
• Orbital apex syndrome/ON/RAPD
• Corneal exposure K
• Paeds: amblyopia/refractive error/astig
• Association
– Systemic/syndrome/phacomatoses

10. Secondary Orbital Tumour
- Local Spread/Metastasis -
Paeds
• Neuroblastoma (26%)
– 1`- neck/abd/mediastinum
– SSx: BL ecchymotic
proptosis, congenital
Horner/heterochromica
– Mx: chemoT > radioT, <1yo
90% survive, >1yo 10%
• Nephroblastoma
• Leukemia >ALL
* more to orbit!
• ON Glioma
• RB
Adults
• Breast > lung >prostate
– palliative/radioT
*more to choroid!
• Eyelid (SCC/BCC/SGC)
• Choroidal melanoma
• Sinus ca/NPC (SCC)
• ON sheath meningioma

11. Orbital- Eyelid Tumour

12. Eyelid Tumour- Classification
• Anatomical layer
– epidermis
– dermis/adnexal/
gland/hair
– subcutaneous
fat/periosteum
– vascular
– nerve
• Characters
– pigmented vs non
– benign vs malignant
– primary vs metastasis

13. Eyelid
Classification
• Pigmented- basal cell (papilloma/seborrheic keratosis/Ca),
freckle (ephelis)/nevus (congenital/acquired)/melanoma
(50% non-pigmented)
• Non pigmented- sq cell (papilloma/ca/actinic keratosis/
Bowen), epidermoid inclusion/epidermoid/dermoid cyst,
xanthelasma
• Vascular (red)- capillary hemangioma, port wine stain,
pyogenic granuloma, Kaposi sarcoma
• Nerve- neurofibroma, Meckel cell ca
• Gland- sebaceous (chalazion/pillar/Zeiss/SGC), sweat (Moll
hydrocytoma/syringoma), hair (comedone/milia/
pilomatricoma), +- infection/ruptured/inflammation

14. Benign epidermal
• Type: SC/BC papilloma, actinic keratosis
• SCP (=skin tag)
– SSX: pedunculated/sessile/filiform +- HPV
– histo: SC a-/hyper-keratosis cover + fibrovascular core
• BCP (=seborrheic keratosis/senile verruca)
– SSX: >elderly, brown plaque (greasy/discrete/stuck-on)
– histo: BC + keratin-filled cyst
– DDX: pigmented tumour (BCC/melanoma/nevus)
• Actinic keratosis (=solar/senile keratosis)
– SSX: hyperkeratotic plaque/horn/wart/nodule → malignant transform
SCC
– histo: keratotic (dysplasia/para/hyper)
– DDX: SCC/SCP/BCP

15. Pigmented Eyelid Tumour
• Basal cell papilloma (seborrheic keratosis)/BCC
• Freckles (ephelis)
– Brown macule 1-5mm @sun exposed area
– Epidermal high melanin/N melanocyte
• Congenital melanocytic nevus
– hairy/kissing/split/15% malignant (if large)
• Acquired melanocytic nevus (3grp JCI: age/sign/histo/malignant)
– junctional (young/macule/btw epi-dermis/low malignant)
– compound (middle age/raised/epi to dermis/low malignant)
– intradermal (old/commonest/no-little pigment + dilated
vessels/dermis only/no malignant)
– atypical mole (AMS)/multiple dysplastic nevus
@skin/lid/conj/uveal naevi → high malignant (melanoma)
• Melanoma
– atypical melanocyte with invasion/Lentigo (in-situ)

16. Malignant Eyelid tumour- General
• SCC
–10%/aggressive mets (LN/perineural V/VII/intracranial)/nodular-ulcer-horn or
keratocanthoma (rapid growth → regress)
– keratin pearl/desmosome/keratosis/no surface vascularization (vs BCC)
–a/w actinic keratosis/Bowen CIS/AIDS/immuno-down/XP
• BCC
– 90%/invasive not mets/>LL & medial/nodular-ulcer-sclerosing/morphoeic
– palisading cell/thin cord
– a/w Gorlin (AD/skeletal), xeroderma pigmentosum (AR)
• SGC
–>F/>asian/old/UL, nodular-spreading-pagetoid, yellow material, pale foamy lipid cell
– +LN (low mets),not sensitive to radioT
• Kaposi sarcoma
–AIDS related vascular tumour (endoT + proliferating spindle cell), radioT sensitive
• Meckel’s MCC
– elderly/rapid grow & mets/>UL/nodular (no ulcer), APUD cell/sensory cell
• Melanoma
– 4 types: Lentigo maligna (Hutchinson freckle/in situ))/superficial spreading/nodular/
acrolentiginous

17. Eyelid/Conj Malignancy- Risk
• General- elderly/fair skin/sun UV/albinism/ocular tumour
• Immunosuppressed- SCC & OSSN
• Preexisting eyelid/skin dz- actinic keratosis/Bowen/nevus
(>congenital melanocytic/AMS)
• Xeroderma pigmentosum (BCC/SCC/melanoma/conj OSSN)
– AR, sunlight damage/hypersensi, bird-like facies
• Gorlin-Goltz (nevus BC syndrome → BCC @2nd decade)
– AD, eye-bone-face-CNS (jaw cyst/falx cerebri Ca/hand
feet pitting), breast Ca/H lymphoma/medulloblastoma
• Muir-Torre syndrome (BCC/SGC/keratocanthoma)
– AD, colorectal/GUT Ca
• Bazex Dupre Christol (BCC)
– XLD, follicular atrophodema skin, hypo-hidrosis-trichosis
• Acrokeratosis paraneoplastica of Bazex
– psoriatic/ezcema, respi/GI Ca
• Ifx- HPV 6/18 (conj sq papilloma/OSSN)

18. Keratoacanthoma
• Neoplasia/premalignant or variant of SCC
(SCC transformation 5%)
• VS SCC = same histopath (sq CIS) & risk, but
different genomic profile
• >middle age/elder,
• Classical: rapid growth (wk-mth) and
stabilization or regress, solitary flesh with
elevated edge and center keratin core
• Surgical excision include the deep
margin/base for HPE

19. Xanthelasma
1. lipid laden histiocyte (foam cells)
@dermis/subcut
2. common/elderly/>F
3. SSX: BL/multiple, >medial,
4. A/W: hyperlipidemia (1/3), cornea arculis
5. Mx (cosmetic): excision, microdissection,
laser/CO2/cryo, 75% trichoroacetic acid
(slow)

20. Dermoid Cyst
1. Choristoma/developmental d/o
2. skin sequestered/displaced ectoderm to subcutaneous
along embryo closure line (>temporal frontal zygomatic)
3. round/film @lateral end of brow (65%), sup nasal (30%)
4. Subcutaneous with mobile under skin/tethered to deep
periosteum
5. Superficial vs deep (septum)
– Deep: >adult >gradual proptosis/dystopia
6. Ix CT: calcification/fluid/fat + bone erosion, wall enhanced
with contrast but not lumen
7. Cx: ruptured/inflam (+- trauma), +- bony defect
8. Mx: excision in toto (encapsule), steroid only if inflam
9. VS epidermoid/inclusion cyst: epidermis → dermis @line
of closure (round/slow/superficial +- rupture/inflam)

21. Chalazion
1. meibomian (sebaceous)/lipo-granuloma
2. SSx: sterile/chronic/painless
3. A/W: rosacea, meibomianitis, conj granuloma
4. Mx: lid hygiene/I&C
5. Mx (recur): doxy 100mg BD 6/52, triamcinolone
1-10mg (rpt 2/52, SE depigment/gland damage)
6. Cx: inflam, infected → hordeolum internum
7. = marginal cyst (Zeis), pilar cyst (cilia/hair)
8. DDx: SGC

22. General treatment
• Biopsy/excision (+HPE/frozen section)
– Incisional
– Excisional (shave/simple/Mohs micro-dissection, 2-4mm margin)
– +- sentinel LN biopsy (esp SGC/melanoma >1mm/Meckel)
• Marsupialization
• Laser/Cryo (liquid nitrogen) ablation
• Chemical peeling (bi-/tri-chroloacetic acid)
• +- reconstruction (suture/graft depends size/FT/lamellar)
–primary closure (<⅓ +- lat canthoplasty)
–ant lamellar: skin advance/flap/graft
–post lamellar: tarsal graft/buccal MM/hard palate/Hughes flap 4-6wk
–secondary intention (Laissez-faire)
–flap (UL: Tenzel/Hugh/Mustande, LL: Cutter-Beards)
• Radiotherapy (> Kaposi/small BCC, not for SGC/medial lesion)
• Enucleation/Exenteration (ocular/orbital/bone)

23. Orbital- Lacrimal

24. Lacrimal Tumour
• Primary
– benign
• Epithelial: pleomorphic adenoma
• Non epithelial: benign proliferative lymphoid hyperplasia
– malignant
• Epithelial
– adenocystic Ca
– pleomorphic adenoCa (malignant mixed tumour)
– sq cell mucoepidermoid Ca
• Non epithelial: lymphoma
• Secondary: direct adjacent vs distant (lymphoma)
• DDX: TB/fungal/Inflam (Sarcoidosis)/CTD (Wegener)

25. Pleomorphic adenoma
• benign epithelial lacrimal tumour (= mixed tumour)
• EpiD: most common/30s/>F
• +- translocation PLGA1 (chr 8q12) @HMGA2 gene
• SSx: gradual/painless
– +- non axial proptosis
– +- ON/CN-palsy
• Ix: CT (pseudocapsule round smooth/bone excavation
indentation = pressure changes)
• Mx: excision (encapsule)
–Incomplete remove- malignant changes (10%)/ recur (30%)
• Histo: fibrous pseudocapsule with Bosselation (microprojection
from capsule to tumour) + ductal mixed element (epithelial +
stroma)
– epithelial: tubule/form nest
– stroma: myxoid/cartilage/bone
– IHC: +ve keratin/epithelial (@ductal/epithelium), +ve
actin/myosin/fibronectin/S100 (@myoepihtelium)

26. Adenoid Cystic Ca
• Epid: 40-50s/>F
• SSx: fast growth/pain (perineural spread)
• Ix: CT (not encapsulated/Ca/bony erosion/nerve
invasion)
• Mx: Incision Bx → remove
• Histo: gross grayish white nodular
– Cribriform (swiss cheese)- most common (5yr 70%)
– Basaloid (solid)- worse prognosis (5yr 20%)
– Comedo/Sclerosing/Tubular
– IHC: +ve S100/keratin/actin

27. Malignant Lacrimal Tumour
Pleomorphic AdenoCa Adenoid Cystic Ca Lymphoma
Age 20-50s >F 40-50s >F >50s
Onset slow >1yr faster <1yr Insidious/acute on
chronic
Pain - + (perineural spread) -
Location UL UL UL/+-BL (17%)
CT Pseudocapsule
Round/smooth @fossa
Bone indentation/
pressure changes
No capsule
Calcification, bone
erosion, nerve invasion
Diffuse (both
orbital/palpebral)
Molded to shape og
globe
Systemic TAP LN
Mx Incisional Bx → Excision
+ radioT → exenteration
Incisional Bx  excision
 exenteration/chemo-
radio
Bx/chemo/radio
Risk Long standing adenoma,
prev incomplete excision
Histo: worse Basaloid >
Cribriform

28. Vascular Tumours

29. Orbital Vascular Tumours
• capillary >paeds
• cavernous >adult
• hemangio-pericytoma –endothelioma
• kaposi sarcoma
• kimura/leiomyoma
• AVM/malform
• lymphangioma
• varix
Key:
1. intermittent proptosis
2. size change (cry/valsalva)
3. pulsation/bruit
4. bleed/hrge

30. Intraocular Vascular Tumours
• Retinal
– capillary hemangioma (esp VHL)
– cavernous hemangioma
– vasoproliferative tumor
– racemose hemangiomatosis (Wyburn–Mason)
• Choroidal
– circumscribed choroidal hemangioma
– diffuse choroidal hemangioma (esp SWS)

31. Cavernous VS Capillary Hemangioma: Similarity
• Most common benign orbital tumour in paeds/adult
• Benign vascular hamartoma/hemangioma
• F>M
• > Sporadic
• Unilateral discolouration lesion/mass
• Proptosis
• ON compression
• No pain/bruit/pulse
• B scan/doppler/CT/MRI
• No calcification/erosion

32. Cavernous VS Capillary Hemangioma:
Difference
Capillary
• Small vessels
• Small age (paeds)
• Fast flow
• Fast growth 3-6m then resolved by 7yo
• Superficial/deep, eatra/intra-conal
• +-axial/non proptosis
• > red (+- h’rge)
• Cry/compress → change
• No change
• > visceral assoc (skin/laryngeal/cns)
• a/w Kasabach Merritt/Maffucci
• Strawberry nevus
• No capsule/septum, poor margin
• endothelial only
• FFA: multiple feeder A&V (rapid flow)
• Rx steroid > excision
Cavernous
• Large vessels
• Large age (adult)
• Slow flow
• Slow growth then hypertrophy
• Deep intraconal
• Axial proptosis
• > pink (no h’rge)
• No change
• Pregnant/hypoxia → change
• No visceral assoc
• a/w SWS
• Yes capsule/septum, good margin
• endothelial + muscle wall + stroma
• Port wine stain
• FFA: no feeder, late stain (low flow)
• Rx observe > excision (capsule)

33. Infantile hemangioma
• Five indications for early treatment of problematic infantile hemangiomas (IHs) include the following:
• Life-threatening lesions, such as those that obstruct the airway, are associated with high-output congestive heart failure or
ulcerative IHs that profusely bleed.
• IHs associated with functional impairment such as disturbance in vision or feeding interference.
• IH ulceration.
• IH-associated congenital anomalies such as PHACE syndrome (large IHs that can cause defects in the eyes, heart, major
arteries, and brain).
• Risk of permanent scarring.
• IH growth most rapidly occurs between 1 and 3 months of age.
• Imaging is not necessary unless the diagnosis is uncertain, there are five or more cutaneous IHs, or there is suspicion of
anatomic abnormalities.
• Oral propranolol (between 2 and 3 mg/kg per dose) is the recommended first-line treatment for cases requiring systemic
therapy.
• Counsel about the adverse events of propranolol such as sleep disturbances, bronchial irritation, and clinically symptomatic
bradycardia and hypotension.
• Use oral prednisolone or prednisone if there are contraindications or if the propranolol response is inadequate.
• Intralesional injection of triamcinolone and/or betamethasone can be recommended to treat focal or bulky IHs in certain
critical locations (eg, the lip) or during proliferation.
• Topical timolol maleate may be prescribed for thin or superficial IHs.
• Surgery and laser therapy may be recommended for certain situations such as ulcerated lesions or lesions that obstruct vital
structures

34. Ocular- Conj/sclera/cornea
(epibulbar or ocular surface tumour)

35. Epibulbar Tumour- Approach
• Hx: HOPI of mass, risk factors, systemic review (mets)
• PE: ocular + LN + systemic
• Mass: number, location, extension (lateral/depth/ext),
size/shape/colour, content (pigmented/solid/cystic/vascular),
surface, surrounding (feeder vessels)
• Ix: photo, ASOCT/UBM, biopsy HPE, cytology
(impression), MRI
• DDX: pigmented vs non, benign vs malignant, primary vs
secondary, epithelium vs stroma (vascular/lymphatic
• Rx: surgery, chemotherapy, immunotherapy, and
radiotherapy

36. Classification (Origin)
• Conjunctival Tumours
– conjunctival epithelium
– conjunctival stroma
– Within the stroma: blood vessels, nerves, fat,
and lymphoid tissue
• Corneal tumours
– Mostly extension of conj tumour
– Epithelium & stroma

37. Classification (Pigment/Malignancy)

39. OSSN
• Epibulbar - non pigmented – epithelial
• Spectrum: CIN – CIS – SCC
• Risk: UV/fair, HIV/HPV, old/male/smoke, xeroderma pigmentosum
• SSx: interpalpebral, gelatinous/ leucoplakic/papilliform, vascular, feeder vessels
• Surgery (no touch)
– Corneal + conj + sclera
– Good wide margin 2-4mm
– Cornea absolute alcohol-assisted epithelium curettage/blade scrapping (avoid Bowman)
– Lamellar sclerectomy
– CryoT
– Ocular surface reconstruction (LSCT, AMT, lamellar keratoplasty)
• Medication/topical chemoT
– Neoadjuvant, adjuvant, primary alternative
– MMC, 5FU,
– IF α2b: least toxic, months (4-6), +- subconj/perilesional (3M IU/0.5ml weekly)
– MMC/5FU: more toxic, shorter durations, MMC >melanocytic, 5FU >Sq

40. subconjunctival injection (3 million units in 1 mL)

42. Dermoid @ Conj
=Choristoma (collagenous tissue/dermal element
(gland/hair)/stratified sq epiT (+- keratinized)
• Limbal dermoid
– childhood, a/w Golderhar/Treacher collins/Linear naevus
sebaceous of Jadasson
–Subconj mass (soft/dome/smooth/yellowish) >inf-tem
– Rx: excision +- lamellar keratosclerectomy (if large)
• Dermolipoma
– adult
– subconj mass (>soft/>yellow) >outer canthus/sup-tem
– + extension (to orbit/limbus)
– Rx: debulking/excision (risk of scar/ptosis/EOM)

43. Limbal Dermoid
• Choristoma (peribulbar mass @ paeds  1/3 is choristoma)
• Variety of aberrant tissues, mesoblast metaplasia or pluripotent cells
sequestration
• Common features: inf temporal corneo-limbal area, superficial,
paeds/<16yo
• Complication: affecting visual axis, astig, lipid infiltration
• Potential risk: deeper extension till AC, malignant transformation- rare
• Systemic association: 30% e.g. Golderhar (eyelid coloboma), Duane
retraction syndrome, SCALP syndrome, NF, nevus flammeus
• Clinical diagnosis  MRI only if unsure extension (EOM, orbital fat)

44. Limbal Dermoid- Treatment
• Superficial sclero-keratectomy (cutting flush with the
surface of the globe) + HPE
• Complete removal unnecessary (+- deep extension 
perforation)
• +- lamellar keratoplasty/patch graft (if deep excision)
• +- AMT (if large bare sclera)

45. Dermoid + Coloboma + Microphthalmia
Craniofacial clefting disorder (part of congenital orbital disorder)
• Goldenhar syndrome (oculoauriculovertebral spectrum)
– Systemic: facial & ear hypoplasia/macrostomia/microtia/skin
tags, hemivertebrae (>cervical), mental/CNS/cardiac/renal
– Ocular: dermoids + eyelid coloboma (UL) + microphthalmos, OD
coloboma, Duane syndrome
• Treacher Collins syndrome (AD)
– Ocular: dermoid + eyelid coloboma (lat 1/3 LL) + microphthalmos,
lacrimal atresia, cataract
– Systemic: facial hypoplasia
• Linear naevus sebaceus of Jadasson.
– Systemic: skin (warty/scaly), infantile spasms, CNS/dev
– Ocular: dermoids + lid colobomas + microphthalmos. , ptosis,
cloudy cornea,, fundus colobomas

46. Pyogenic Granuloma
• benign vascular proliferation of immature capillaries that is neither
purulent nor granulomatous
• is also called lobular capillary hemangioma
• Misnomer: no inflammatory (purulent) exudate nor the typical epitheloid
giant cell reaction/granulomatous inflammation.
• Microscopically, aggregations of immature blood vessels and fibroblastic
stroma (granulation tissue), with accompanying lymphomcytes, plasma cells, and
scattered neutrophils.
• Early PG: have numerous capillaries and venules with prominent
endothelial cells arrayed radially toward the epithelial surface.
• Mature PG: exhibits a fibromyxoid stroma separating the lesion into
lobules. The epithelial surface exhibits inward growth at the base of the lesion.
• Regressing PG: has extensive fibrosis
• Classical: well circumscribed, smooth surfaced, pink, sessile/pedunculated,
and highly vascularized mass, underlying stalk of feeder blood vessels and
connective tissue
• Eyelids, conjunctival, rarely limbus/cornea
• Traumatic wound site or near a suture line  rapid growth <few wks)

47. Ocular- Uveal

48. Uveal Tumour
• Uveal: arise from mesoderm
• Classification: pigmented VS non-pigmented
• Pigmented/Melanocytic:
– feckles (high melanin but normal melanocyte)
– melanocytoma (cell with melanin filled granules)
– benign nevi
– malignant melanoma
– Pigmented tumour (fr pigmented epiT)
• Non pigmented:
– amelanotic melanoma
– inflammatory granuloma
– secondary metastasis

49. Uveal Nevus
• Iris (stroma)
– 2 forms: circumscribed (+-nodular) or diffuse (entire/sectoral)
– a/w NF/Cogan Reese @ICE/ectropion iridis/sectoral cataract
– DDX: melanoma (+growth), CB tumour (if angle)
• CB
– identified if + extrascleral extension → subconj fixed mass/angle tumour
• Choroidal
– 10% population +- amelanotic
– flat/mild elevated (<1mm) + indistinct margin + size <10mm
– a/w RPE disturbance/drusen/CNV
– Malignant changes 1/400 (enlargement)- risk: Sx/orange pigment/SRF/
juxtapapillary, no drusen/RPE changes, hot spot in FFA
– DDX: melanoma (size >10mm, thickness >3mm), melanocytoma
– DDX: RPE hyperpigmentation @hemangioma/metastatic Ca/CHRPE/AMD,
osteoma, suprachoridal h’rge

50. Uveal Melanoma
• Iris
– 10% uveal melanoma, ¾ inf iris, > periphery
– variant: amelanotic → dark brown, solid →
diffuse/heterochromia
– SSx: growth (size/thickness)/vascularity (feeder)/ ectopion
uvea/extrascleral extension
• hyphaema/cataract/glaucoma (angle seed)
– Mx: identified extension! → post border-gonio-UBM-AS OCT
– Rx: Bx (FNAC/in-excision), brachyT/radioT (low mortality 10%)
• CB
– 12% uveal melanoma
–undetected/asym → large/extension (lens displaced/angle &
glaucoma/AC/epibulbar) → 180-360 ring melanoma
– SSx: sentinel vessel
• cataract/glaucoma/RD/iris NV
• Choroidal

51. Choroidal Melanoma
• most common primary intraocular malignancy @adult, 75% of uveal melanoma
• EpiD: 50-60s, >light skin (15x)/blue eye/blonde hair
• Risk: ocular/oculodermal- melanocytosis (Ota), dysplastic nevus syndrome/AMS, NF1, smoking, UV,
genetic p53 (chr 7)
• SSx
– pigmented/elevated/dome shaped → collar stud/mushroom (break Bruch) +- amelanotic
– orange pigment (lipofuscin@RPE), feeder vessel, SRD, SRH/VH
– ant segment: uveitis/cataract/glaucoma
– systemic: liver > lung > breast mets, locally to ON/brain
– VS Nevus = PED/drusen/CNV/VF/orange pigment
– VS Nevus ≠ lipofuscin/orange pigment (but no drusen), near OD, size >2mm thick, Cx e.g. RD/SRF, hot spot in FFA,
histo +epithelioid cell
• B scan
– high reflective border
– low internal reflectivity/acoustic hollowness → DDX choroidal hemangioma (high) & choroidal mets (variable)
– Choroidal excavation (high spike d2 Bruch break)
– Orbital shadowing
– Extraocular extension
• FFA- double circulation (choroid/retina vessels), hyper (RPE destruction), hypo (lipofuscin mask)
• Other: CT/MRI/Bx & Callender classification - spindle A (nevus) → +spindle B (melanoma) → + epithelioid
(worst, morta 75%), usually mixed (86% cases/morta 50%)
• Mx: depends VA/size/location/extend-mets, COMS, laser photocoag → brachyT → enucleation (+-radioT)

52. Risk factor for malignant transformation
• “To Find Small Ocular Melanoma Using
Helpful Hints Daily” (TFSOM-UHHD)
– thickness > 2 mm (most important!)
– subretinal fluid
– Symptoms
– orange pigment present
– margin within 3 mm of the optic disc
– ultrasonographic hollowness (versus solid/flat),
– absence of halo (pigmented choroidal nevus
surrounded by a circular band of depigmentation.)
– absence of drusen

53. Collaborative Ocular melanoma Study (COMS)
• Small (1-3mm thick, <5mm long) @1989
–natural history/observe: 30% +growth in 5yr
–mortality: 6% 5yr, 15% 8yr → photoCoag
• Medium (3-8mm thick, <16mm long) @1998
–enucleation VS brachyT (iodine 125 gold
plaque/85Gy)
–survival: same (82% @5yr) → brachyT
• Large (8mm thick, >16mm long) @1994
–enucleation alone VS pre-radiation (ext
beam/20Gy)
–survival: same (60% @5yr) → enucleation

54. Brachytherapy
• Ruthenium-44
– 7mm penetration
• Iodine-125
– 10mm penetration

55. Iris Mammillations- DDX
= multiple/tiny/regular spaced villiform dark
lesions
• Oculodermal melanocytosis (Ota)
• NF1
• AXS
• Peter’s

56. Melanotic Terminology
• Melanocyte- dendritic cell @ epidermis (basal
layer), conj epithelium, uveal tissue.
• Melanin- substance secreted by melanocyte
• Melanosome- cellular organelle produce
melanin
• Malanophage- macrophage engulfs melanin
• Nevus- atypical melanocyte forming nest of cells
(no dysplasia)
• Melanosis- abn production of melanin (N
melanocyte)

57. Lymphoproliferative D/O
• Lymphoid hyperplasia (benign)
• Lymphoma
• Histiocytic d/o
• Xanthogranuloma
• Plasma cell tumour (MM/plasmacytoma)
• Lymphoepithelial infiltration (Sjogren/Mikulicz)

58. Ophthalmic Lymphoma
Types
• Ocular adnexal/orbital lymphoma (20% of orbital tumour)
– Orbit
– Lids
– Lacrimal gland (50%, >a/w systemic lymphoma)
– Conjunctiva
• Intraocular lymphoma
– Uveal (rare/>secondary)
– Vitreo-retina (>primary/CNS lymphoma)
General
• PathoP: Infection/inflammation-Mutation Model (IMM)
• SSx: slow/no pain/no symptoms
• Orbital- 30% before 30% after systemic lymphoma (need systemic workup)
• Ocular- primary VR CNS lymphoma (need LP/brain imaging & systemic
workup)
• Biopsy: flow cytometry, immunohistochemistry, cell surface marker, PCR
• CD 20 for B cell, CD 3 for T cell
• IL10-IL 6 ratio)
• steroid Rx will change the HPE of lymphoma

59. Orbital Lymphoma
• Intro: 20% of orbital tumour
• Risk: age/chemical exposure/autoimmune dz (chronic)
• Systemic lymphoma- 30% prior & 30% aft
• Key feature: UL/painless/progress (BL 17%)
– salmon patch (conj)
– eyelid S-shaped/firm rubbery mass/
– +- ptosis/proptosis/EOM/diplopia
• Ix: (staging/CT/Bx)
– Staging: blood/CXR/BMAT/neck TAP CT or PET
– CT scan mold to structure (rarely EOM/ON d/o, if +invasion=high grade)
– Bx: fresh sample (cell surface marker/flow cytometry/PCR/microscope)
• Mx:
– Orbital only: radioT 25Gy (+- Rituximab)
– If systemic: chemo/radioT (+-debulking)

60. Orbital/Adnexal Lymphoma
5keys
• Extranodal
• Non Hodgkin
• B cell (95%)
• Bone marrow derived/Homing mechanism
• Multifocal (not metastasis)
5 common types
• Extranodal marginal zone EMZL (most)
• Diffuse large cell DLCL (high grade)
• Follicular FL
• Mantle cell ML
• Small cell/lymphoplasmatic LPL (high grade)
* Other class (REAL)- MALT/small cell/follicular/high grade
(large cell/Burkitt/lymphoplastic)

61. Intraocular Lymphoma
• Types/location
• VR
• > primary & a/w CNS lymphoma (>common/aggressive/non
Hodgkin/extranodal/Bcell/large cell)
• If 2nd to VR > Hodgkin’s type (rare)/>chorioretinitia
• Uvea (rare)
• > 2nd/metastatic dz (similar to adnexal lymphoma)
• Primary VR lymphoma
– EpiD: >50/UL  BL
– SSx: PanU, white retinitis >subretinal with Cx (RPE
clump/vasculitis/RVO/RAO/RD/OD, but rarely CMO)
• + dense vitritis
• + AC reaction (+white eye hypopyon)
• + CNS SSx (brain/spine/meningitis)
– Ix (eye): FFA (leopard skin), vitreous/TPPV tap/Bx, subretinal Bx
– Ix (sys)-:LP, MRI brain/orbit
– Mx: (depend laterality/CNS involvement)
• Ocular: IVT MTX/radioT if UL, IV MTX/IVT MTX/radioT if BL (IV poor
penetration/>recurrence)
• Systemic/CNS: IV MTX/chemoT
• New: biological agent (rituximab)
– Prognosis: poor

62. Histocytosis X/Langerhans cell
• Intro: abn dendritic histiocyte/mononuclear
phacocyte
• EpiD: >peads (5-10yo)
• SSx:
– Spectrum of severity- spontaneous resolution 
dissemination/death
– Orbital inflam: relapsing/lytic bone lesion (orbit/sphenoid
wing)/proptosis (sup temporal)
• Mx: Bx  debulking/steroid injection/low dose radioT
 chemoT (if systemic)
• Prognosis: worse if <2yo (50% survive), >2yo (90%
survive)
• Variant: juvenile xanthogranuloma (non Langerhans
histiocytic lesion/self limit/steroid sensitive)

63. Xanthogranuloma
• Intro: systemic (+orbital) lymphoid tumour
• 4 syndromes
– Necrobiotic X
– Adult onset X
– Adult onset asthma with periocular X
– Erdheim-Chester dz (ECD: @adult/worse)
– Variant: juvenile xanthogranuloma
• Systemic: paraproteinemia/MM, LN,
fibrosclerosis of pleural/fascial

64. Phakomatosis

65. Phacomatosis/Neurocutaneous
+ systemic (CNS/skin) & ocular tumour +
1. NF
2. SWS
3. VHL
4. TSC
5. Wyburn Mason
6. Incontinenta pigmenti
7. Ataxia telangiectasia
* Glaucoma: NF (rare) & SWS (30%)
* Inherited except SWS & WM
* AD except IP (XL) & AT (AR)

68. Neurocutaneous syndromes/Phakomatoses
Four major disorders with important ocular manifestations:
• neurofibromatosis 1 (von Recklinghausen disease)
• tuberous sclerosis (Bourneville disease)
• angiomatosis of the retina and cerebellum (von Hippel-Lindau disease)
• encephalofacial or encephalotrigeminal angiomatosis (Sturge-Weber
syndrome)
Others
• ataxia-telangiectasia (Louis- Bar syndrome)
• incontinentia pigmenti (Bloch-Sulzberger syndrome)
• racemose angioma (Wyburn-Mason syndrome)
• Klippel-Trenaunay-Weber syndrome

69. NF-1 (peripheral/Von Recklinghausen)
• AD (incomplete) + FHx*/sporadic- chr 17
• Affect > peripheral/autonomic nerve (not motor)
• Skin x3: café au lait (>5)* @1yo, anxillary/inguinal freckles* @10yo, neurofibroma
(>1)*
• CNS x3: neurofibroma/glioma/schwannoma (epilepsy/HCP/mental challenge)
• MSK: short, scoliosis, facial hemiatrophy, sphenoid bone defect or dysplasia *
• Others: pheochromocytoma (high BP)
• Eye x 6 (major):
– Orbital/eyelid plexiform neurofibroma (S-shape/bag of worm/ptosis)
– Prominent corneal nerve
– Iris Lisch nodule (>1) * 95%/10-20s
– Retinal hamartoma/astrocytoma (=TSC)
– Choroidal hamartoma/nevi/melanoma
– Optic nerve/chiasma/pathway glioma *33%/young children (axial/non pulsatile proptosis,
opticiliary shunt, fusiform)
• Eye (minor x3):
– Spheno-orbital encephalocele (non axial/pulsatile proptosis)
– Ectopion uvae
– Glaucoma (rare, > UL/congenital, a/w plexiform neurofibroma of upper lid @50%/iris/CB
neurofibroma obstruction/angle abn)
• Diagnostic criteria: atleast 2/7 *

70. NF2 (central/vestibular schwannoma)
• Less common, AD/sporadic, Chr 22
• Less café au lait
• Eye:
– CNP (5-8 @ CP angle)
– PSCC/CC @66%
– No Lisch, no glaucoma
– Yes retinal/RPE hamartoma
• Diagnostic criteria:
– BL schwannoma/acoustic neuroma 90% or
– FHx + UL schwannoma or 2/4
(meningioma/glioma/schwannoma/juvenile CC PSCC)

71. TSC
• AD, chr 9
• Skin x 6: adenoma sebaceum, periungual fibroma, Ash-
leaf spot, Shagreen patch, skin tag, café au lait
• CNS: astrocytoma/glioma (epilepsy/HCP/mental
challenge)
• Eye:
– Astrocytoma
– Iris hypopigmentation
– Fundus hypopigmentation
• Others: visceral hamartoma (kidney/heart)

72. SWS
• = encephalotrigeminal angiomatosis
• Sporadic (non hereditary)
• Skin: nevus flammeus (port wine stain/cavernous
hemangioma) @V1/V2, hemifacial hypertrophy
• CNS: pial meningeal angioma (parietal/occipital, +- calcify
with tram tract sign)- epiplepsy/hemiparesis/hemianopia
• Eye (ipsi with PWS):
– Glaucoma 30% (esp upper lid involved)
• 60% before 2yo (+- buphthalmos)
• Pathophysio: episcleral venous pressure/angle abn/CB hemangioma
– Choroidal hemangioma 40% (>diffuse)
– Episcleral/iris/CB hemangioma (+- lens subluxation)
– PWS with ptosis

73. VHL
• AD, Chr 3
• Skin: café AL, melanocytic nevi
• CNS: hemangioblastoma
• Eye: retinal capillary hemangioma (need
laser/cryo/PDT/antiVEGF)
• Others: pheochromocytoma (HPT), visceral
cysts (kidney/liver/lung/ovary)

74. Ataxia telangiectasia
• AR, Chr 11
• Skin: telangiectasia
• CNS: cerebellar ataxia, mental challenge
• Eye:
– Conj telangiectasia
– Cerebellar nystagmus/oculomotor defect/squint

75. Incontinentia Pigmenti
• X linked dominant
• Skin 3 stages: erythema/bullae @limbs →
wart → hyperpigment/christmas tree pattern
@trunk
• CNS: epilepsy, mental challenge, HCP
• Eye:
– Proliferative retinopathy (DDX ROP)

76. Wyburn Mason
• Sporadic (non hereditary)
• CNS: AVM
• Eye: Racemose angioma

77. Other Associations with Systemic Malignancy
• Ophthalmic Metastasis
• Intracranial tumour (pituitary/optic
pathway)
• Paraneoplastic syndrome
• MEN 2B

78. Eye problem @systemic cancer
• Ocular metastasis
• Paraneoplastic syndrome
• Compression by tumour
• Infection secondary to chemoT
• Radiation complication (retinopathy)

79. Ophthalmic Metastasis
• Ocular > Orbit (& lids & conjunctival)
• Ocular: uvea > others
• Uvea: choroid > others
• Choroid: macular/peri-macular area > others
• Classical red flag: creamy yellow, elevated mass deep to the retina in the choroid +- symptoms
• Breast > lung > others
• Eye presentation before cancer: Lung > breast
• Lung vs Breast eye mets: breast >multiple > bilateral, lung +-pain
• Theory of “shower of mets to brain” – a/w brain mets (40%)
• Vs primary amelanotic melanoma: mets <thick (2-3mm vs 5-5mm), >yellow >homogeneous, <RPE
changes, >echogenic
• Others: ERD, OD swelling, hypopyon/panU
• Rx  only for tumour threatening vision
– Multifocal/bilateral- ext beam radiation (OD for 4wk)
– Multifocal/bilateral/solid single- plaque radioT (2days)
• Important of ophthal assessment: first presentation before tumour, ocular Rx for vision
threatening, monitor response of systemic Rx

80. Breast Ca
• Metastatic foci of the disease in the lungs,
central nervous system, or bones are usually
detected prior to diagnosis of ocular
metastases
• risk of fellow eye involvement is
estimated to be 5% in a period of ten months
after diagnosis

81. Choroidal Mets
• Can be 1st sign of systemic malignancy in
1/3 cases
• Up to 10% of cancer +uvea mets (breast &
lung)
• Fundoscopy, ultrasonography (US), and
fluorescein angiography, indocyanine green
angiography (ICGA), optical coherence
tomography (OCT), Histopathological by
choroidal tumor biopsy

82. Choroidal Mets

83. Visual paraneoplastic syndromes
• Circulating antibody affecting retinal protein
(cross reaction with tumour antigen)
• carcinoma-associated retinopathy
• melanoma-associated retinopathy
• bilateral diffuse melanocytic uveal
proliferation
• paraneoplastic optic neuropathy (PON)
• The first affects photoreceptors, the second
is thought to affect bipolar cell function, and the
third targets the uveal tract

84. Multiple endocrine neoplasia (MEN) type 2B
• AD (chr 10q11)
• medullary carcinoma of the thyroid gland,
pheochromocytoma, and mucosal neuromas
• marfanoid habitus, thickened corneal
nerves, conjunctival and eyelid neuromas and
keratoconjunctivitis sicca

85. Paraneoplastic Syndrome (PNS)
• Def: cancer-related SSx
– not related to mass effect but due to
– humoral (hormone/cytokine) from tumour, or
– immune reaction to tumour
• Common sources: lung, breast, ovaries, lymphoma
• Types:
– Neurological: Lambert Eaton/MG (small cell lung ca), myositis,
spinal cord, CNS
– Hematological: low/high RBC/Hb/hypercoagulopathy
– Endocrine: high Ca/ACTH-Cushing/ADH-SIADH/insulin-hypoG/
aldosterone/carcinoid (serotonin)
– Muco-cutaneous
– Ocular: retinopathy (CAR/MAR)
• Ix: autoimmune Ab (anti-Hu/Ri/Yo/Ma/Amphiphysin/CVS)
from IMR, whole body CT scan/PET

86. Paraneoplastic retinopathy
CAR (cancer-associated retinopathy)
– Ab against recoverin/retinal protein
– Peripheral + central visual loss (rapid/progress)
– Arterial narrowing with only min/no pigment
– ERG- Extinguished
MAR (melanoma-associated retinopathy)
– ERG- negative waveform
Others
– Autoimmnue retinopathy
– BDUMP (BL diffuse uveal melanocytic proliferation)-
choroidal lesion + ERD + PSCC + iris/CB cyst
– acute exudative polymorphous vitelliform maculopathy